Present test systems for examining environmental agents are elaborate and time consuming. Short term screening procedures which will be efficient and informative are urgently needed. The present proposal has as its objective the development of reliable test systems employing both prokaryotes and eukaryotes, in order to evaluate the correlation between carcinogenicity and mutagenicity. Specifically, we will: 1) determine the mutagenicity of a variety of carcinogens; 2) determine the type or genetic alteration produced by these carcinogens; 3) measure the initiating capability of these carcinogens and model mutagens in the mouse-skin tumor induction system; 4) compare the relative efficiency of mutagenic agents as initiators, as a function of the type of mutation they cause; e.g., frameshift or point; 5) apply virus, yeast and human white cells as test organisms in the host-mediated assay in mice; 6) measure changes in physical properties and RNA polymerase priming activity in homogeneous circular mitochondrial DNA isolated from rat liver. The unusual toxicity by some environmental agents causing cancer a decade or more after exposure fits readily into the concept of a heritable alteration caused by the agent, which is expressed at the time of onset of the diseases. The identification of the type of mutations most closely related to carcinogenesis may aid in providing a rapid and reliable predictive test system for evaluation of environmental agents to which man may be exposed. It is also believed that these studies will advance our understanding of the fundamental biochemical processes involved in carcinogenesis.